Topical Glucocorticoid Use and the Risk of Posttransplant Diabetes.

Systemically administered glucocorticoids constitute an essential part of the immunosuppressive regimen for transplant recipients, yet their known risks of causing hyperglycemia or posttransplant diabetes require close monitoring and minimisation of use, when possible, to prevent detrimental effects on patient morbidity and graft survival. Topical glucocorticoids, on the other hand, are rarely considered to affect glucose metabolism and therefore seldomly monitored, despite their wide and in some cases, long-term use. We report a case of a renal transplant recipient presenting with acute hyperosmolar hyperglycemia after treatment with topical glucocorticoids and present a mini review of the literature.

Kidney transplantation from an HIV-positive deceased donor to an HIV-positive recipient.

Preliminary data on HIV-positive donor to HIV-positive recipient kidney transplantation suggest promising patient outcomes without adverse events. This is an important step in expanding the donor pool and opportunity for transplantation in HIV-positive patients.We herein report the first case of HIV-positive donor to HIV-positive recipient kidney transplantation in Denmark. Our patient has demonstrated a successful post-transplant course with excellent 1-year graft function, no rejection episodes, good virological control with undetectable HIV RNA, no signs of HIV-associated nephropathy, and no superinfections or opportunistic infections.This case corroborates findings from previous studies showing that kidney transplantation from carefully selected HIV-infected donors to carefully selected HIV-infected recipients seems to be a safe and effective treatment option, and supports the opportunity to expand the organ donor pool for this group of patients with end-stage renal disease.

Short-term Outcome of Danish Kidney Donors: Postoperative Complications and Labor Affiliation.

BACKGROUND: Living kidney donation is safe and effective, but disincentives to donation include risk of short- and long-term complications, which need to be addressed in order to ensure care of live kidney donors. METHODS: From January 1, 2016 to December 31, 2019, 123 living kidney donors (LKDs) underwent LKD nephrectomy at Aarhus University Hospital, Aarhus, Denmark. Data from The Scandiatransplant registry and patient records were reviewed in order to identify short-term postoperative complications within 90 days after donation, as well as affiliation to the labor market and health data at follow-up. The Clavien-Dindo classification of surgical complications with modifications by Kocak et al was used to categorize minor and major complications. RESULTS: There were available data for 119 of 123 LKDs. Of these, 25 (21%) developed minor complications and 4 (3%) developed major complications. Ninety LKDs (76%) had an uneventful course without any complications. The most common complications were pain and nausea that required additional medical treatment. Seventy-two of the 82 LKDs working before donation had returned to work within 3 months after donor nephrectomy. No one retired or became disabled as a result of being a live kidney donor. CONCLUSIONS: Short-term follow up of the LKDs showed that most donors experienced an uneventful course and that the frequency of major complications was low. Donation did not seem to impact the ability to resume work. At the 90-day follow-up the majority of donors with both minor and major complications resumed work and reported full convalescence at the same level as donors without any complications. Nine of the LKDs (8%), all women, were out of work for >3 months with the main reason being fatigue.

Eculizumab treatment of thrombotic microangiopathy in a patient with ulcerative colitis.

Secondary thrombotic microangiopathy (TMA) can be induced by several underlying conditions and drugs, yet coexistence of TMA and inflammatory bowel disease (IBD) has only infrequently been documented. A successful management beyond supportive care in cases with secondary TMA represents a challenge, as some underlying conditions might amplify complement dysregulation or even unmask a genetic predisposition to atypical hemolytic uremic syndrome (HUS)-both of which could require treatment with a complement blocking agent. We observed a case in which TMA developed in a patient with ulcerative colitis (UC). Genetic screening showed a heterozygous mutation in diacylglycerol kinase ε (DGKE). Eculizumab resulted in complete resolution of TMA, however UC relapsed after cessation of eculizumab.

The effects of calcineurin inhibitors on prostanoid synthesis: a randomized cross-over study in healthy humans.

The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus (Tac) are implicated in post-transplant complications such as cardiovascular morbidity. Prostanoids are fatty acid-derived compounds essential for controlling cardiovascular homeostasis. We tested the hypothesis that CNIs suppress cyclooxygenase (COX)-2-derived prostacyclin (PGI) and increase thromboxane synthesis in humans. Ten healthy men underwent 5-h infusions of CsA, Tac, and saline in a randomized, double-blind, cross-over study. Blood and urine samples were collected before and after the infusion of each drug/saline, to measure PGI and thromboxane metabolites. CsA decreased whole-blood COX-2 activity by 39% (P = 0.05) and basal plasma 6-keto-PGF(1α) levels by 31%, only nonsignificantly. Urine excretion of PGI-M and TxB(2) did not change significantly after CsA infusion. Tac decreased TxB(2) in the COX-1 ex vivo assay by 30% (P = 0.03), while no changes were seen in urinary levels of PGI-M or TxB(2) . Urinary TxB(2) excretion was 15% lower after saline infusion (P = 0.03). These within-treatment differences in prostanoid synthesis did not differ significantly between the treatments (anova). Mean blood levels of CNIs were 486 µg/l for CsA and 12.8 µg/l for Tac. Clinically relevant doses of CsA and Tac induce acute differential changes in prostanoid levels in healthy human subjects. CsA suppresses COX-2 activity, while Tac decreases platelet activity.

Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: New onset diabetes after transplantation is related to treatment with immunosuppressive medications. Clinical studies have shown that risk of new onset diabetes is greater with tacrolimus compared with ciclosporin. The diabetogenicity of ciclosporin and tacrolimus has been attributed to both beta cell dysfunction and impaired insulin sensitivity. WHAT THIS STUDY ADDS: This is the first trial to investigate beta cell function and insulin sensitivity using gold standard methodology in healthy human volunteers treated with clinically relevant doses of ciclosporin and tacrolimus. We document that both drugs acutely increase insulin sensitivity, while first phase and pulsatile insulin secretion remain unaffected. This study demonstrates that ciclosporin and tacrolimus have similar acute effects on glucose metabolism in healthy humans. AIM The introduction of calcineurin inhibitors (CNIs) ciclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) cause impairment of survival rates. The relative contribution of each CNI to the pathogenesis and development of NODAT remains unclear. We sought to compare the impact of CsA and Tac on glucose metabolism in human subjects. METHODS: Ten healthy men underwent 5 h infusions of CsA, Tac and saline in a randomized, double-blind, crossover study. During infusion glucose metabolism was investigated using following methods: a hyperinsulinaemic-euglycemic clamp, an intravenous glucose tolerance test (i.v.GTT), glucose-stimulated insulin concentration-time series and indirect calorimetry. RESULTS: Clamp derived insulin sensitivity was increased by 25% during CsA (P < 0.0001) and 13% during Tac administration (P = 0.047), whereas first phase and pulsatile insulin secretion were unaffected. Coinciding with the CNI induced improved insulin sensitivity, glucose oxidation rates increased, while insulin clearance rates decreased, only non-significantly. Tac singularly lowered hsCRP concentrations, otherwise no changes were observed in circulating glucagon, FFA or adiponectin concentrations. Mean blood concentrations of CNIs were 486.9 ± 23.5 µg l(-1) for CsA and 12.8 ± 0.5 µg l(-1) for Tac. CONCLUSIONS: Acute effects of i.v. CsA, and to a lesser degree Tac infusions, in healthy volunteers include increased insulin sensitivity, without any effect on first phase or pulsatile insulin secretion.